Toxicogenomic Responses of Zebrafish Embryos/Larvae to Tris(1,3-dichloro-2-propyl) Phosphate (TDCPP) Reveal Possible Molecular Mechanisms of Developmental Toxicity

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Abstract

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is frequently present in indoor dust and can be detected in human milk. In order to evaluate the effects of TDCPP on vertebrate development, zebrafish embryos/larvae were used as an animal model to examine developmental phenotypes and explore possible mechanisms of toxicity by employing microarrays and iTRAQ labeling quantitative proteomics. The results demonstrated that treatment with TDCPP (3 μM) from 0.75 h postfertilization (hpf) inhibited cell rearrangement at 4 hpf, caused delay in epiboly at 5.7 and 8.5 hpf, and led to abnormal development (e.g., short tail, reduced body size) and lethality between 14 and 45 hpf, which might be related with altered expression of genes regulating embryogenesis. Furthermore, trunk curvature was observed as the main phenotype in 96 hpf zebrafish larvae exposed to 1 or 3 μM TDCPP, possibly by changing somite formation and expression of proteins related to fast muscle and cartilage development. Collectively, our results suggest that exposure to TDCPP causes developmental toxicity in vertebrates and warrant the need for studies to evaluate the potential health risks of TDCPP to developing human embryos/infants/children, due to its frequent presence in indoor dust and potential for human exposure.

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